Summary Cell Structures and functions

Cells are a basic unit of life, sharing many common mechanisms across different classes
of organisms (plants, animals, microorganisms). Between these classes there are also key
differences in cell architecture.
In a cell, the external bilayer (plasma membrane) and the nuclear membrane are built
and maintained by lipids. Stiff protein filaments (microtubules and actin filaments) confer
rigidity to the cells cytoskeleton.
The rate of production of proteins (gene regulation) is controlled by many factors,
including the physical forces acting on a cell and the cells mechanical environment.
In animal cells a network (polymer gel) of actin filaments is the key element in cell
motility as it is stiff enough to exert forces that deform the cell membrane.

These are introductory lectures, setting the stage for other aspects of the lecture course. It
would be possible to treat the topics described here much more quantitatively, if these
lectures were given after a set of polymer physics lectures. The books by Nelson,and by
Phillips et al. are excellent guides through a more quantitative analysis. The book by
Alberts et al. is one of the most common biology textbooks on cells and is updated almost
yearly to reflect current understanding. It is striking to a physicist how in biology even a
first-year standard textbook requires substantial and frequent revision.

The cell is a basic unit for life forms. As well as enabling sophisticated control of
biochemical processes by providing compartments and regulating chemical fluxes between
them, cells also have structural integrity and can exert forces. In the case of multicellular
organisms (animals and plants), each cell contributes some mechanical property to the
tissue it forms together with other cells. Furthermore, many cells are eliminated during the
life of a complex organism (e.g. skin layers in animals), which entails cell division and
restructuring of the organisation with neighbours. Some types of cell are actually very
motile, moving through tissues (e.g. various immune system cells and some cancer cells).
This dynamic aspect is even more obvious during the development of multicellular
organisms, when many stages of cell division and migration take place.

How a cell maintains its structure and the ability to move or react to external forces is a
fascinating aspect of cell biology in which physics modelling and experimenting are
proving very successful. This lecture and the next introduce some basic physics of cell
structures.

1.1 Cell components

A first division of organisms is between those whose cells have within them a nucleus, the
structure containing most of the genetic material in the form of DNA, and those whose cells
dont. The nucleated cells are called eukaryotic and are found in animals, plants, fungi,
protozoa and algae. In contrast, bacteria (and the less common archaea) do not have a
nucleus and their DNA is spread throughout the cell. These cells are called prokaryotic.
Eukaryotic organisms can be unicellular or multicellular while all prokaryotes are
unicellular.

Aside from the distribution of DNA, there are other very obvious differences between
eukaryotic and prokaryotic cells. At a coarse level the size, and at the level of molecular
detail the chemical detail of proteins used in the two classes of organisms is quite different.
(This is what allows certain antibiotics to interfere at the molecular level with essential
processes in bacteria, while not affecting the functioning of the cells of an animal.)

Within the nucleated cells there are structural differences between animal and plant cells. A
standard biology textbook illustration of an animal eukaryotic cell is shown in Slide 2. In
animals, cells can often secrete protein fibres and complex sugar molecules
(polysaccharides). These mesh together at the molecular scale, making an elastic material
known as extracellular matrix (ECM). Some cell types reside at a particular place in the
organism (e.g. the epithelium) while others are motile through the ECM (e.g. immune
system cells).

From a materials point of view, it is useful to distinguish clearly structures that are
essentially built and regulated by lipids: the external bilayer (plasma membrane), the
nuclear membrane and various other organelles in the cell, such as the Golgi complex and
the endoplasmic reticulum, which play key roles in the assembly of proteins. (For more on
lipid bilayers and membranes, see the topic Elements of Statistical Mechanics and Soft
Condensed Matter, Lecture 5 Lipid bilayers and Lecture 6 Fluctuating membranes.) In
contrast, microtubules and actin filaments are structures assembled of proteins

A point that should fascinate any physical scientist is the degree of control that has evolved
in order to achieve conditions in which both lipid and protein structures can self-assemble
(not to mention the sophisticated mechanisms to make use of and preserve the DNA genetic
code).

While the biochemical functioning of cells depends on proteins (essentially many of a cells
functions can be understood as proteins performing chemical reactions), these proteins
live attached to lipid membranes, or confined by lipid compartments. The physical
properties of the lipids are thought to contribute to the regulation of protein biochemistry,
but this is still not fully clear.

Which structures are stiffest?

Lipid membranes are generally soft, meaning that they easily deform due to thermal
fluctuations, although energies greater than the thermal kBT are needed to bend lipid
bilayers. (Lipid bilayers and membranes are also discussed in lectures 5 and 6 of the
Statistical Thermodynamics topic.) In contrast with lipid structures, we can identify protein
structures, in particular the filaments called microtubules (made of the protein tubulin,
polymerised together) and actin filaments (made of the protein actin). These form the cells
cytoskeleton and are quite stiff, in the sense that thermal energy is not sufficient to bend
them significantly on the scale of a cell radius: they are straight rods.

Slide 4 shows a prokaryotic cell, which has a simpler architecture than a eukaryotic cell,
but many common aspects in both structure and function. It compares and contrasts these
two types of cell. Bacteria are probably the most important type of prokaryotic organism.
Note in particular the absence of a nuclear membrane: here the DNA is spread throughout
the cell. All bacteria are single-cell organisms (although to understand their evolution, and
how they survive, it only makes sense to consider their collective behaviour in a colony).
Many bacteria, under appropriate nutrient conditions, can replicate extremely quickly (the
bacterium E. coli can duplicate every 20 minutes, in contrast with fast eukaryotic division,
which may only occur every 24 hours), giving rise to an exponential increase in cell
number with time.

1.2 Cell processes

Cells regulate their behaviour and their function by controlling the concentration (in some
cases it may be small numbers) of different proteins. Some proteins perform a function
themselves, whereas others serve to control protein production rates. (See the lectures in the
topic Regulatory Networks.) This network of interactions is analogous to a computing
machine, and, indeed, cells can compute. However, the circuit is not hard set. It is not
enough to know the genetic code since the cell behaviour will also depend most importantly
on the concentration of all proteins, but also on other factors among which are the
conformation of the DNA and the composition of lipids in the membranes. There is recent
evidence that forces acting on a cell, and more generally the mechanical environment
around a cell, can affect the process of gene regulation, maybe one day offering new
opportunities to exploit stem cells for regenerative medicine. Before looking at how this
might work, it is useful to review very briefly the essential processes that take place in a
cell.

Cells contain DNA, which is a sequence of amino-acid bases. The cells in a human all have
the same DNA but are clearly very different. About 200 different cell types are classified in
a human (bone, skin, blood, muscle, etc.). The differences between cells (biologists would
call this the phenotype) are due to each being in a different steady state of protein
expression. Proteins are constantly being made (see below) and degraded in a cell. The rate
of production is finely controlled, involving a sophisticated interplay between binding
constants determined by detailed protein structures, and statistical physics

Despite much research in the medical and biological communities, and joined by increasing
numbers of physicists and engineers, it is still not fully understood how this fine level of
control of the steady state is achieved. (Also see the topic Biological Molecules Lecture 1
The structure of DNA and RNA.) This is a key question, the importance of which is clear
if we think of stem cells . These are cells, present in all multicellular organisms (at least
during some stage of their development from single cell embryos), that are in a state from
which they are able to differentiate into any other cell type. Clearly they have the same
genetic material as any other cell, and yet they have the unique property of easily becoming
other cell types. Understanding better how they maintain their special non-differentiated
state, and also the cues (which may be chemical or mechanical) that control their
differentiation fate, could allow breakthroughs in the treatment of various diseases.

Short sequences of DNA containing the information sufficient to describe a protein

sequence (a gene) are copied (by a protein machine called RNA polymerase) into RNA.
This process is known as transcription.

There are subtle different functions for the RNA, but the main one is for these RNA
sequences (in this case calledmessenger-RNA: mRNA) to be made into proteins. This
process, through which the RNA code is read, and translated into a sequence of residues
to make a specific protein, is called translation and involves a protein machine called the
ribosome.

Proteins are the main workhorses of a cell: they do things either in isolation or by
assembling with multiple units of each other, or of different proteins. The combinations are
almost endless. (See Biological Molecules, Lecture 3 Proteins.) As a general principle,
cells need to have different proteins at different times, and also they need to use the energy
and materials at their disposal efficiently. For both reasons the production of each type of
protein is regulated.

This regulation of gene expression happens most importantly at the transcription stage,
since this is the first stage and hence it is most efficient to take regulating action there. The
main process of regulation involves RNA polymerase binding to DNA in order to start
transcription, and this binding affinity can be controlled by certain proteins known as
transcription regulation factors. So by making a few more regulation factor proteins, a
cell can tune how many of various other proteins to make.

There is also regulation at the other stages, with subtle but important effects, for example,
on the control of noise, and these are ideas still under investigation. (For more detail, see
Regulatory Networks Lecture 3 Biochemical Noise.) The general picture outlined here
(the central dogma of molecular biology, Slide 5) is one of the most important ideas in cell
biology because it is general and applies to all cells. It has been elucidated by the brilliant
work of many people during the decades since the discovery of DNA structure

1.3 Cell mechanics and processes

1.3.1 Interplay of forces and structures

As noted above, there is evidence that forces acting on a cell, and its general mechanical
environment, can affect protein formation and hence the process of gene regulation. How
this takes place is still not known, but the most obvious issues to consider are whether the
external force has an effect on the binding of some transcription factor, or on the production
rate of some other important intermediate molecule.

Much better accepted is the idea that a cell has mechanical stability and can exert forces on
the surroundings (Slide 6). Processes such as motility and adhesion to a substrate require
dynamic control of the architecture. There are three main types of semiflexible filaments in
eukaryotic cells, made from different proteins, and they differ substantially in their
resistance to bending. The filaments have many roles in the cell: providing mechanical
stability; facilitating directional intracellular transport (they are tracks for motors);
anddetermining the symmetric separation of the nucleus and cell during cell division,
enabling cell motility. Slide 6 shows the three main types of filament that perform these
functions. In Slide 6, lp is the persistence length that is, the distance along the rod over
which the direction (statistically) changes.